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Couper, J.J.* ; Oakey, H.* ; Penno, M.A.S.* ; Wentworth, J.M.* ; Watson, K.A.* ; Brown, J.D.* ; Huynh, D.* ; Thomson, R.L.* ; Craig, M.E.* ; Davis, E.A.* ; Haynes, A.* ; Huynh, T.T.* ; Vuillermin, P.J.* ; Soldatos, G.* ; Lopez, P.E.* ; Morahan, G.* ; McGorm, K.* ; Kim, K.W.* ; Barry, S.J.* ; Hamilton-Williams, E.E.* ; Rawlinson, W.D.* ; Sinnott, R.* ; Harrison, L.C.* ; Achenbach, P. ; Colman, P.G.*

Evolution of islet autoantibodies in the Environmental Determinants of Islet Autoimmunity (ENDIA) prospective cohort.

Diabetologia, DOI: 10.1007/s00125-025-06591-4 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
AIMS/HYPOTHESIS: Islet autoantibodies herald early type 1 diabetes. However, less is known of the evolution of autoantibodies to the islet autoantigen ZnT8. Our primary aim was to characterise the development of islet autoantibodies in a pregnancy-birth at-risk cohort and to provide new knowledge about ZnT8A. METHODS: Islet autoantibodies were measured every 3-6 months in 1277/1473 children with a first-degree relative with type 1 diabetes who were followed prospectively from pregnancy in the Environmental Determinants of Islet Autoimmunity (ENDIA) cohort for 7.0 (IQR 5.8-8.3) years. Islet autoantibodies were also measured in the mothers and/or in cord blood in 901 pregnancies with type 1 diabetes. RESULTS: The development of persistent IAA reached a probability of 0.02 by 2 years of age. A combination of IAA- and GADA-first, GADA-first and ZnT8A-first all reached a similar probability by 5 years of age. ZnT8A appeared as the first islet autoantibody, alone or in combination, in 43 (32%) of the 134/1473 children with persistent islet autoantibodies. Persistent single ZnT8A, detected only by ELISA, usually appeared after 4 years of age. ZnT8A that progressed to multiple islet autoantibodies or type 1 diabetes were detected in younger children (p=0.006) and in multiple assay formats. ZnT8A were confirmed in additional assay formats when present with multiple islet autoantibodies, but not when remaining as a single islet autoantibody, unlike IAA and GADA. Maternal islet GADA were detected until 15 months of age and transmission of any islet antibody/autoantibody did not relate to islet autoantibody development in the offspring (χ2=3.32, df=2, p=0.19). CONCLUSIONS/INTERPRETATION: Persistent single ZnT8A, which are detected only by ELISA and no other test format, appear not to confer an increased risk of progression to type 1 diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Children ; Islet Autoantibodies ; Type 1 Diabetes ; Znt8 (zinc Transporter 8); Risk; Heterogeneity; Progression; Definition; Assay
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Grants National Health and Medical Research Council
Juvenile Diabetes Research Foundation Australia
Leona M. and Harry B. Helmsley Charitable Trust